Isopropanol → tert-Butyl (4-{(1S,2R)-2-{[(5,5-dimethyl-2-phenyl-1,3-dioxan-2-yl)methyl]thio}-1-[(4-fluorophenyl)amino]-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetate

HRID 254085Notes

Reaction equation

HRID 254085 reaction equation
[CH3:1][C:2]1([CH3:31])[CH2:7][O:6][C:5]([CH2:14][S:15][CH2:16][C:17]([N:19]2[C@@H:23]([C:24]3[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=3)[CH2:22][O:21][C:20]2=[O:30])=[O:18])([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:4][CH2:3]1.[F:32][C:33]1[CH:38]=[CH:37][C:36]([N:39]=[CH:40][C:41]2[CH:55]=[CH:54][C:44]([O:45][CH2:46][C:47]([O:49][C:50]([CH3:53])([CH3:52])[CH3:51])=[O:48])=[CH:43][CH:42]=2)=[CH:35][CH:34]=1.C(N(C(C)C)C(C)C)C.C(O)(C)C>C(Cl)Cl.CC([O-])C.CC([O-])C.CC([O-])C.CC([O-])C.[Ti+4].Cl[Ti](Cl)(Cl)Cl.O>[CH3:1][C:2]1([CH3:31])[CH2:3][O:4][C:5]([CH2:14][S:15][C@@H:16]([C:17](=[O:18])[N:19]2[C@@H:23]([C:24]3[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH2:22][O:21][C:20]2=[O:30])[C@H:40]([C:41]2[CH:55]=[CH:54][C:44]([O:45][CH2:46][C:47]([O:49][C:50]([CH3:51])([CH3:52])[CH3:53])=[O:48])=[CH:43][CH:42]=2)[NH:39][C:36]2[CH:35]=[CH:34][C:33]([F:32])=[CH:38][CH:37]=2)([C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[O:6][CH2:7]1

Participants

9

Reactant 4

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 66842977(4S)-3-({[(5,5-Dimethyl-2-phenyl-1,3-dioxan-2-yl)methyl]thio}acetyl)-4-phenyl-1,3-oxazolidin-2-oneHCID 86619087Tert-butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate

Product 1

HCID 86619086tert-Butyl (4-{(1S,2R)-2-{[(5,5-dimethyl-2-phenyl-1,3-dioxan-2-yl)methyl]thio}-1-[(4-fluorophenyl)amino]-3-oxo-3-[(4S)-2-oxo-4-phenyl-1,3-oxazolidin-3-yl]propyl}phenoxy)acetateYield 56.3%

Reagents, catalysts & solvents 4

HCID 11026Titanium isopropoxideCatalystHCID 24193Titanium TetrachlorideCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolvent4×

Conditions

Temperature
-30 °C

Procedure

Tetraisopropyl orthotitanate (0.51 ml, 1.8 mmol) was added to a solution of TiCl4 (1M in CH2Cl2, 5.1 ml, 5.1 mmol) in CH2Cl2 (50 ml) at 0° C. under inert atmosphere. The mixture was stirred for ten minutes. (4S)-3-({[(5,5-Dimethyl-2-phenyl-1,3-dioxan-2-yl)methyl]thio}acetyl)-4-phenyl-1,3-oxazolidin-2-one (3.0 g, 6.8 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 20 minutes. After ten minutes, tert-butyl (4-{[(4-fluorophenyl)imino]methyl}phenoxy)acetate (4.5 g, 13.6 mmol) in dry CH2Cl2 (50 ml) was added dropwise over 30 minutes. The mixture cooled to −30° C. and stirred for 20 minutes. Ethyl diisopropyl amine (2.3 ml, 13.4 mmol) in 20 ml dry CH2Cl2 was added dropwise over ten minutes and the mixture was stirred at −30° C. for six hours. The mixture was cooled to −78° C. Isopropanol (60 ml) was added and the temperature was risen overnight. H2O (100 ml) was added and the mixture was stirred for 35 minutes at room temperature. The mixture was extracted twice with diethyl ether. The combined organic layers were washed with water, dried (MgSO4) and concentrated under reduced pressure. Purification by flash-chromatography (hexane:EtOAc 5:1) afforded 2.95 g (56%) of the title compound as a yellow solid. M/z: 793.3 (M++Na).

Workup

  1. waitAfter ten minutes
  2. stirringstirred for 20 minutes
  3. stirringthe mixture was stirred at −30° C. for six hours
  4. temperatureThe mixture was cooled to −78° C
  5. stirringthe mixture was stirred for 35 minutes at room temperature
  6. extractionThe mixture was extracted twice with diethyl ether
  7. washThe combined organic layers were washed with water
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated under reduced pressure
  10. customPurification by flash-chromatography (hexane:EtOAc 5:1)

Sources & evidence

ORD record
ord-3d80f7b57df3452ca9ce0f83e3618866
Source dataset
uspto-grants-2011_01
Patent number
US07871998B2

Reaction notes

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